Acral Lentiginous Malignant MelanomaPhase 2NCT00470470
Imatinib Mesylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
A Phase 2 study testing imatinib mesylate and laboratory biomarker analysis in people with Acral Lentiginous Malignant Melanoma and Recurrent Melanoma, run by National Cancer Institute (NCI) at 8 sites in United States.
Trial summary
This phase II trial is studying how well imatinib mesylate works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acral Lentiginous Malignant Melanoma, Recurrent Melanoma, Stage IIIA Melanoma
- What is being tested?
- imatinib mesylate and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 8 sitesUnited States
- Study dates
- Apr 2007to Oct 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed inoperable stage III or IV melanoma that began on acral skin or mucosa
- Patients with cutaneous melanoma that began on sun exposed sites of the skin and whose pathology demonstrates signs of sun damage (solar elastosis) involving the skin surrounding their primary melanoma are eligible
- Must have sufficient tumor tissue available for FISH and DNA sequencing
- Patients must have either a true amplification of 4q12 or a detectable mutation of c-KIT
- If no banked tumor tissue is available, or if the available banked tumor tissue is insufficient for the necessary testing, then a repeat biopsy procedure will be required to collect the necessary tumor sample
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Show all 45Show fewer
- No known untreated brain or epidural metastases
- Brain metastases that have been treated and deemed stable are allowed
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Life expectancy greater than 3 months
- WBC ≥ 3,000/mm³
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Patients with unexplained hyperbilirubinemia that is clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert's syndrome) may be eligible
- AST and ALT ≤ 2.5 times ULN (5 times ULN if hepatic metastases are present)
- Creatinine ≤ 1.5 times ULN
- PT and PTT ≤ 1.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception before and during study participation
- No history of allergic reactions attributed to compounds of similar chemical or biological composition to imatinib mesylate
- No concurrent uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable anginapectoris
- Cardiac arrhythmia resulting in hemodynamic instability
- Intestinal malabsorption disorders
- Psychiatric illness or social situations that would limit study compliance
- Recovered to grade 1 from all prior therapies with the exception of alopecia
- At least 2 weeks since prior radiotherapy (≤ 3,000 cGy to fields including substantial marrow)
- At least 2 weeks since prior isolated limb infusion or perfusion (must have evidence of progression despite this therapy)
- At least 2 weeks since prior chemotherapy
- No more than 2 prior chemotherapy regimen for metastatic melanoma
- Prior therapies with vaccines, targeted agents not believed to affect the kit proteins, cytokines, interferon-α, or intratumoral injections will NOT be considered prior therapy unless administered with a chemotherapy drug
- No prior therapy with an inhibitor of the kit protein
- No other concurrent investigational agents
- No other concurrent anticancer agents or therapies
- No concurrent antiretroviral therapy for HIV-positive patients
- No concurrent inhibitors of CYP3A4, including any of the following:
- Fluconazole, itraconazole, ketoconazole, macrolide antibiotics (azithromycin, clarithromycin, erythromycin, troleandomycin),midazolam, nifedipine, verapamil, diltiazem, terfenadine, cyclosporine and cisapride
- Herbal extracts and tinctures with CYP3A4 inhibitory activity, including the following:
- Hydrastis canadensis (goldenseal), Hypericum perforatum (St. John's wort),Uncaria tomentosa (cat's claw), Echinacea angustifolia roots, Trifolium pratense(wild cherry), Matricaria, chamomilla (chamomile), Glycyrrhiza glabra (licorice), dillapiol, hypericin, and naringenin
- No concurrent inducers of CYP3A4, including any of the following:
- Carbamazepine, phenobarbital, phenytoin, and rifampin
Who cannot join
None listed.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of California at Los Angeles (UCLA )
Los Angeles, California, 90095
Mount Sinai Medical Center CCOP
Miami Beach, Florida, 33140
New York University Langone Medical Center
New York, New York, 10016
Mount Sinai Medical Center
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Weill Medical College of Cornell University
New York, New York, 10065
Good Samaritan Medical Center
West Palm Beach, Florida, 33401
Palm Beach Cancer Institute-Main Office
West Palm Beach, Florida, 33401
About this study
Official title: A Phase II Study of Imatinib Mesylate (STI571;NSC#716051:IND 61135) in Patients With Inoperable AJCC Stage III or IV Melanoma Harboring Somatic Alterations of C-KIT
This phase II trial is studying how well imatinib mesylate works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the overall objective response rate (complete response and partial response) in patients with inoperable stage III or IV melanoma harboring somatic alterations in c-KIT treated with imatinib mesylate.
SECONDARY OBJECTIVES:
- Determine the time to progression in patients treated with this drug. II. Determine if c-KIT mutational status by DNA sequencing, DNA copy number status by fluorescent in situ hybridization (FISH) or comparative genomic hybridization, and/or protein expression by immunohistochemistry (IHC) can best predict clinical benefit from imatinib mesylate.
TERTIARY OBJECTIVES:
- To evaluate tumors resistant to small molecule inhibitors of Kit for the development of secondary Kit mutations or for changes in Kit copy number.
II. To evaluate for changes in Ki-67, phospho-Akt, phospho-MEK, phospho-S6, phospho STAT3, cleaved caspase 3, IGF-1R, and Kit expression in paired tumor samples obtained from patients treated with a small molecule inhibitor of Kit.
III. To analyze baseline and post-resistance blood samples for soluble cKIT levels, soluble VEGFR1, soluble VEGFR2, VEGF, PlGF, FGF, and melanoma inhibitory activity (MIA) levels, and circulating tumor cells.
IV. To analyze concomitant samples of blood and tumor for imatinib levels in patients treated with imatinib.
OUTLINE: This is a multi-center study. Patients are stratified according to true amplification of c-KIT by FISH vs mutations by DNA sequencing.
Patients receive oral imatinib mesylate twice daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity.
Tumor tissue samples or unstained tissue slides/paraffin blocks may be collected. c-KIT is evaluated by IHC and comparative genomic hybridization.
After completion of study treatment, patients are followed up periodically.
- Conditions
- Acral Lentiginous Malignant Melanoma, Recurrent Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IV Melanoma
- Being tested
- imatinib mesylate, laboratory biomarker analysis
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
imatinib mesylateDrug
Also called CGP 57148, Gleevec, Glivec
Given orally
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Patients receive oral imatinib mesylate twice daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: imatinib mesylate; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
Response will be evaluated in this study using the new international criteria proposed by the RECIST Committee. A Simon two-stage minimax design will be employed.
Measured: Every 6 weeks for the first 3 courses and then every 12 weeks thereafter
Secondary outcomes (1)
Time to Progression
Progression will be evaluated in this study using the new international criteria proposed by the RECIST Committee. Time to progression will be estimated using the Kaplan-Meier method.
Measured: Time from the treatment start to the date of disease progression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2007 (estimated)
- Study startApr 2007
- Primary completionDec 2013
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acral Lentiginous Malignant MelanomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Richard Carvajal, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00470470
- Sponsor's protocol ID
- NCI-2009-00216
- Other IDs
- NCI-2009-00216, CDR0000543404, MSKCC-07014, 07-014, 7754, P30CA008748, N01CM62206, N01CM62204
- Status last verified
- Jan 2014
- First submitted
- 3 May 2007
- Last updated
- 23 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, Panageas KS, Busam KJ, Chmielowski B, Lutzky J, Pavlick AC, Fusco A, Cane L, Takebe N, Vemula S, Bouvier N, Bastian BC, Schwartz GK. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011 Jun 8;305(22):2327-34. doi: 10.1001/jama.2011.746.
PubMed 21642685
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Imatinib Mesylate (STI571;NSC#716051:IND 61135) in Patients With Inoperable AJCC Stage III or IV Melanoma Harboring Somatic Alterations of C-KIT
- ClinicalTrials.gov ID
- NCT00470470
- Acronym / sponsor ID
- NCI-2009-00216
- Conditions
- Acral Lentiginous Malignant Melanoma, Recurrent Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IV Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Apr 2007
- Primary completion
- Dec 2013 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 7 May 2007 (estimated)
- Results
- Posted 23 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well imatinib mesylate works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- Determine the overall objective response rate (complete response and partial response) in patients with inoperable stage III or IV melanoma harboring somatic alterations in c-KIT treated with imatinib mesylate.
SECONDARY OBJECTIVES:
- Determine the time to progression in patients treated with this drug. II. Determine if c-KIT mutational status by DNA sequencing, DNA copy number status by fluorescent in situ hybridization (FISH) or comparative genomic hybridization, and/or protein expression by immunohistochemistry (IHC) can best predict clinical benefit from imatinib mesylate.
TERTIARY OBJECTIVES:
- To evaluate tumors resistant to small molecule inhibitors of Kit for the development of secondary Kit mutations or for changes in Kit copy number.
II. To evaluate for changes in Ki-67, phospho-Akt, phospho-MEK, phospho-S6, phospho STAT3, cleaved caspase 3, IGF-1R, and Kit expression in paired tumor samples obtained from patients treated with a small molecule inhibitor of Kit.
III. To analyze baseline and post-resistance blood samples for soluble cKIT levels, soluble VEGFR1, soluble VEGFR2, VEGF, PlGF, FGF, and melanoma inhibitory activity (MIA) levels, and circulating tumor cells.
IV. To analyze concomitant samples of blood and tumor for imatinib levels in patients treated with imatinib.
OUTLINE: This is a multi-center study. Patients are stratified according to true amplification of c-KIT by FISH vs mutations by DNA sequencing.
Patients receive oral imatinib mesylate twice daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity.
Tumor tissue samples or unstained tissue slides/paraffin blocks may be collected. c-KIT is evaluated by IHC and comparative genomic hybridization.
After completion of study treatment, patients are followed up periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Drug: imatinib mesylate, Other: laboratory biomarker analysisPatients receive oral imatinib mesylate twice daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (45 listed)
- Histologically or cytologically confirmed inoperable stage III or IV melanoma that began on acral skin or mucosa
- Must have sufficient tumor tissue available for FISH and DNA sequencing
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- No known untreated brain or epidural metastases
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| imatinib mesylateAlso: CGP 57148, Gleevec, GlivecGiven orally | Drug | Treatment (enzyme inhibitor therapy) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (enzyme inhibitor therapy) |
Primary outcome
Objective Response Rate
Time frame: Every 6 weeks for the first 3 courses and then every 12 weeks thereafter
Response will be evaluated in this study using the new international criteria proposed by the RECIST Committee. A Simon two-stage minimax design will be employed.
1 secondary outcome
Time to Progression
Time frame: Time from the treatment start to the date of disease progression
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21642685Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, Panageas KS, Busam KJ, Chmielowski B, Lutzky J, Pavlick AC, Fusco A, Cane L, Takebe N, Vemula S, Bouvier N, Bastian BC, Schwartz GK. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011 Jun 8;305(22):2327-34. doi: 10.1001/jama.2011.746.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Carvajal principal investigator
Memorial Sloan Kettering Cancer Center
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing imatinib mesylate and laboratory biomarker analysis in people with Acral Lentiginous Malignant Melanoma and Recurrent Melanoma, run by National Cancer Institute (NCI) at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 45 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: Every 6 weeks for the first 3 courses and then every 12 weeks thereafter). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00470470, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2014.